The retention and distribution of inhaled aerosols is determined primarily by aerodynamic size of the particles which in turn depends on their physical properties. Many therapeutic and hazardous aerosols are heterodisperse and unstable making analysis of aerodynamic size distribution using conventional methods difficult. We have developed the single particle aerodynamic relaxation on time (SPART) analyzer which determines aerodynamic size distribution in real time over 0.1-10.0 micron m size range at a sizing rate of 40 particles/sec. We have used an improved version of this analyzer along with a climate-controlled aerosol chamber to measure the aerodynamic size distribution of commonly used therapeutic aerosols and to determine the effect of humidity on particle size. We have also done preliminary studies of retention of therapeutic aerosols and of the size distribution of cigarette smoke. In this study we will continue our work on size analysis of therapeutic aerosols and on the size distribution of cigarette smoke and will begin extensive studies on aerosol retention in human subjects. The SPART analyzer will be combined with a climate-controlled inhalation chamber now under construction for studies to evaluate total retention and aerodynamic size of retained aerosol and also the effect of particle hygroscopicity, charge, and respiratory pattern or retention. Therapeutic aerosols will be delivered to subjects in monodisperse forms and as the heterodisperse aerosol produced by clinically used nebulizers. Patients with tracheostomies will be studied to evaluate retention in the upper and lower respiratory tract. A dog model will be developed for sampling of aerosol from peripheral airways to assess aerosol transport to the lung periphery. In summary, we will study size, retention and distribution of unstable heterodisperse therapeutic and hazardous aerosols (cigarette smoke) in human subjects and evaluate the effect of size, hygroscopicity, charge, and respiratory pattern on retention.